Immunotherapy, including gene therapy, for metastatic melanoma.
Current standard therapy for distant metastatic melanoma is ineffective and often compromises the quality of a patient's life. Immunotherapy is briefly reviewed in relation to its many forms: from local non-specific to the more recent specific vaccines, including those using specific melanoma peptides (e.g. from the proteins encoded by melanoma-associated gene (MAGE)) and those involving genetically transduced autologous melanoma cells using retroviral vectors in vitro. The mode of action of genetically transduced melanoma cells incorporating the granulocyte macrophage colony stimulating factor (GM-CSF) gene (GVAX) is presented as a paradigm for cytokine-mediated strategies. Trials of GVAX and other cytokine gene strategies are under way in Brisbane, Boston and Amsterdam, and some interim perspectives on the clinical outcomes and immunological mechanisms involved are sketched. Some of the compounding problems in immunotherapeutic strategies for cancer are identified, and possible adjunct manoeuvres for overcoming them are discussed.
O'Rourke
M G
MG
Mater Adult Public Hospital, Queensland, Australia.
Schmidt
C W
CW
O'Rourke
T R
TR
Ellem
K A
KA
D000951:Antigens, Neoplasm; D001500:BCG Vaccine / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive; D016246:Lymphocytes, Tumor-Infiltrating / Q000637:transplantation; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000627:therapeutic use; D011788:Quality of Life; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D000951:Antigens, Neoplasm; D001500:BCG Vaccine; D019496:Cancer Vaccines; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor